Efficacy of histotripsy combined with rt-PA in vitro.

Efficacy of histotripsy combined with rt-PA in vitro.
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DOI:
10.1088/0031-9155/61/14/5253
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发表时间:
2016-07-21
影响因子:
3.5
通讯作者:
Holland CK
Holland CK
中科院分区:
工程技术2区
文献类型:
--
作者:
Bader KB;Haworth KJ;Shekhar H;Maxwell AD;Peng T;McPherson DD;Holland CK

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组织破坏术是一种利用微泡云的机械作用进行消融溶解的治疗性超声形式,正在开发用于治疗慢性深静脉血栓形成(DVT)。我们假设,联合使用溶栓剂和组织破坏术将增强凝块溶解。重组组织纤溶酶原激活剂(rt-PA)和rt-PA-负载回声脂质体夹带八氟丙烷微泡(OFP t-ELIP)与高冲击组织碎石脉冲组合使用。完全回缩的猪静脉凝块具有DVT闭塞的相似特征,暴露于单独的组织碎石脉冲(峰值负压为7-20 MPa)、组织碎石和OFP t-ELIP或组织碎石和rt-PA。在组织破坏暴露期间,用被动空化成像监测微泡云活动。凝块内空化发射的功率水平在治疗类型之间没有统计学差异,可能是由于OFP t-ELIP的几乎瞬时破裂和缺失。rt-PA可明显提高溶栓效果。这些结果表明,组织破坏术和rt-PA的组合可以作为治疗DVT的有效治疗策略。
Histotripsy, a form of therapeutic ultrasound that uses the mechanical action of microbubble clouds for ablation lysis, is under development to treat chronic deep vein thrombosis (DVT). We hypothesize that combining thrombolytic agents with histotripsy will enhance clot lysis. Recombinant tissue plasminogen activator (rt-PA) and rt-PA-loaded echogenic liposomes that entrain octafluoropropane microbubbles (OFP t-ELIP) were used in combination with highly shocked histotripsy pulses. Fully retracted porcine venous clots, with similar features of DVT occlusions, were exposed either to histotripsy pulses alone (peak negative pressures of 7–20 MPa), histotripsy and OFP t-ELIP, or histotripsy and rt-PA. Microbubble cloud activity was monitored with passive cavitation imaging during histotripsy exposure. The power levels of cavitation emissions from within the clot were not statistically different between treatment types, likely due to the near instantaneous rupture and deletion of OFP t-ELIP. The thrombolytic efficacy was significantly improved in the presence of rt-PA. These results suggest the combination of histotripsy and rt-PA could serve as a potent therapeutic strategy for the treatment of DVT.
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